Massachusetts General Hospital Center for Cancer Research, Department of Pathology, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Genes Dev. 2012 Jul 15;26(14):1515-9. doi: 10.1101/gad.197434.112.
Mutations in the SPRED1 (Sprouty-related protein with an EVH [Ena/Vasp homology] domain 1) and NF1 (neurofibromatosis 1) genes underlie clinically related human disorders. The NF1-encoded protein neurofibromin is a Ras GTPase-activating protein (GAP) and can directly limit Ras activity. Spred proteins also negatively regulate Ras signaling, but the mechanism by which they do so is not clear. In the July 1, 2012, issue of Genes & Development, Stowe and colleagues (pp. 1421-1426) present evidence that Spred1 recruits neurofibromin to the membrane, where it dampens growth factor-induced Ras activity, providing a satisfying explanation for the overlapping features of two human diseases.
SPRED1（具有 EVH [Ena/Vasp 同源性]结构域 1 的 Sprouty 相关蛋白）和 NF1（神经纤维瘤病 1）基因突变是导致临床相关人类疾病的基础。NF1 编码的神经纤维瘤蛋白是 Ras GTP 酶激活蛋白（GAP），可直接限制 Ras 活性。Spred 蛋白也可负向调节 Ras 信号转导，但具体机制尚不清楚。在 2012 年 7 月 1 日的《基因与发育》杂志上，Stowe 及其同事（第 1421-1426 页）提供了证据表明 Spred1 将神经纤维瘤蛋白募集到细胞膜上，从而抑制生长因子诱导的 Ras 活性，这为两种人类疾病的重叠特征提供了一个令人满意的解释。
